Comparison of the Novel Oral Anticoagulants Apixaban, Dabigatran, Edoxaban, and Rivaroxaban in the Initial and Long-Term Treatment and Prevention of Venous Thromboembolism: Systematic Review and Network Meta-Analysis.

BACKGROUND: Anticoagulation with low molecular weight heparin and vitamin K antagonists is the current standard of care (SOC) for venous thromboembolism (VTE) treatment and prevention. Although novel oral anti-coagulants (NOACs) have been compared with SOC in this indication, no head-to-head randomised controlled trials (RCTs) have directly compared NOACs. A systematic review and network meta-analysis (NMA) were conducted to compare the efficacy and safety of NOACs for the initial and long-term treatment of VTE. METHODS: Electronic databases (accessed July 2014) were systematically searched to identify RCTs evaluating apixaban, dabigatran, edoxaban, and rivaroxaban versus SOC. Eligible patients included adults with an objectively confirmed deep vein thrombosis (DVT), pulmonary embolism (PE) or both. A fixed-effect Bayesian NMA was conducted for outcomes of interest, and results were presented as relative risks (RR) and 95% credible intervals (Crl). RESULTS: Six Phase III RCTs met criteria for inclusion: apixaban (one RCT; n = 5,395); rivaroxaban (two RCTs; n = 3,423/4,832); dabigatran (two RCTs; n = 2,539/2,568); edoxaban (one RCT; n = 8,240). There were no statistically significant differences between the NOACs with regard to the risk of 'VTE and VTE-related death. Apixaban treatment was associated with the most favourable safety profile of the NOACs, showing a statistically significantly reduced risk of 'major or clinically relevant non-major (CRNM) bleed' compared with rivaroxaban (0.47 [0.36, 0.61]), dabigatran (0.69 [0.51, 0.94]), and edoxaban (0.54 [0.41, 0.69]). Dabigatran was also associated with a significantly lower risk of 'major or CRNM bleed' compared with rivaroxaban (0.68 [0.53, 0.87]) and edoxaban (0.77 [0.60, 0.99]). CONCLUSIONS: Indirect comparisons showed statistically similar reductions in the risk of 'VTE or VTE-related death for all NOACs. In contrast, reductions in 'major or CRNM bleed' for initial/long-term treatment were significantly better with apixaban compared with all other NOACs, and with dabigatran compared with rivaroxaban and edoxaban. Results from the current analysis indicate that the NOACs offer clinical benefit over conventional therapy while highlighting relative differences in their bleeding profile.

Prevalence and predictors of lipid abnormalities in patients treated with statins in the UK general practice.

OBJECTIVE: To identify the prevalence and predictors of lipid abnormalities in statin-treated patients in the UK. METHODS: A retrospective cohort study was performed using the UK General Practice Research Database. Patients >or=35 years of age were included if they received first-ever statin between January 2000 and December 2004, received statins for at least 6 weeks, had >2 years of pre- and 1 year of post-statin initiation database history, received no concomitant lipid lowering drugs and had at least one complete lipid profile conducted within 1 year before and after initiating statins. Predictors of each lipid abnormality were determined using random effects logistic regression. RESULTS: Within 1 year of statin initiation, 34.7%, 27.4%, 68.2% and 57.6% of patients did not reach optimal levels of TC, LDL-C, HDL-C and TG, respectively. Failure to attain TC goal was explained by smoking (odds ratio=1.13, 95% confidence interval [1.02-1.23]) and baseline TC >6.2mmol/L (5.01, [4.58-5.48]). Failure to attain LDL-C goal was associated with smoking (1.28, [1.14-1.43]), LDL-C >or=4.1 to <4.9mmol/L (2.72, [2.45-3.03]) and LDL-C >or=4.9mmol/L (8.54, [7.62-9.54]). High CHD risk was associated with low HDL-C in women at follow-up (1.94, [1.51-2.48]). Elevated TG was associated with baseline TG >or=2.2 to <5.6mmol/L (4.19, [3.81-4.59]), TG >or=5.6mmol/L (16.10, [3.67-70.57]), smoking (1.26, [1.11-1.42]) and hypertension (1.12, [1.01-1.23]). CONCLUSION: While TC and LDL-C management appear appropriate in the UK, attainment of recommended levels of HDL-C and TG remains poor. The latter remains a concern, as poor attainment of recommended levels of HDL-C and TG is associated with high CHD risk in women, smoking and hypertension.

Assessment of the use of angiotensin receptor blockers in major European markets among paediatric population for treating essential hypertension.

This study was conducted to assess the use of angiotensin receptor blockers (ARBs) in European paediatric patients experiencing essential hypertension. This was a retrospective analysis of the IMS MIDAS Prescribing Insight Medical Database. Five major important European markets, including France, Germany, Italy, Spain and the UK were studied for the usage of ARBs as either a monotherapy or fixed-dose combination (FDC) therapy . Paediatric patients with essential hypertension were identified using ICD-10 codes, and anatomical therapeutic chemical (ATC) classification was used to identify major classes of antihypertensives. Projected prescription data for paediatric patients (<18 years) in the time period of October 2005 to September 2006 were analysed. Special emphasis was placed on the category of 6-17 years of age, as many ARBs were recommended in children above 6 years of age. Out of 242,405 estimated paediatric patients with hypertension, 222,033 (91.6%) were diagnosed with essential hypertension. Out of 230,220 projected prescriptions dispensed in these essential hypertensives, approximately 76.2% were for patients in the category of 6-17 years of. In the age group of 6-17 years, ARBs constituted 25.5% of the projected prescriptions, with 10.6% in the form of FDC of ARBs with hydrochlorothiazides (HCTz). Projected ARB prescription usage, either as a monotherapy or as an FDC with HCTz, was higher in Italy (35.7%), France (30.9%) and Spain (28.1%), but was lower in Germany (5.3%), and non-existent in the United Kingdom. Valsartan-based and losartan-based FDCs were commonly used in the age range of 6-17 years, and accounted for 39. and 13.9% of the projected prescription volume in the ARB-FDC category, respectively. In a majority of the important European markets, paediatric hypertensive patients in the age range of 6-17 years are often treated with ARB monotherapy or FDC therapy. Some ARBs lack necessary clinical studies to support its use in treating essential hypertension in paediatric patients.

Topical phenytoin treatment of stage II decubitus ulcers in the elderly.

OBJECTIVE: To compare the healing of stage II decubitus ulcers with topically applied phenytoin sodium with two other standard topical treatment procedures in a long-term care setting; and to assess the extent of systemic absorption after topical application in the phenytoin group. METHODS: Forty-seven nursing home patients with stage II decubitus ulcers were chosen for this study. The patients were matched for age, gender, and size and severity of wounds, and randomly assigned to each treatment group. Clinical assessment of decubitus ulcers was performed at the beginning of treatment and at each dressing change. Ulcers were examined for the presence of healthy granulation tissue, reduction in surface dimensions, and time to healing. Two phenytoin sodium plasma concentrations were to be obtained on all patients in the phenytoin group. RESULTS: Topical phenytoin therapy resulted in a shorter time to complete healing and formation of granulation tissue when compared with DuoDerm dressings or triple antibiotic ointment applications (p < or = 0.05). The mean +/- SD time to healing in the phenytoin group was 35.3 +/- 14.3 days compared with 51.8 +/- 19.6 and 53.8 +/- 8.5 days for the DuoDerm and triple antibiotic ointment groups, respectively. Healthy granulation tissue in the phenytoin group appeared within two to seven days in all subjects. Patients in the standard treatment groups required six to 21 days to produce new granulation tissue. Serum phenytoin sodium concentrations were nondetectable. No patient withdrew from the study secondary to adverse treatment effects. CONCLUSIONS: Both the phenytoin and standard treatment groups showed progress over the study period. However, the phenytoin group demonstrated more rapid results in all aspects of ulcer healing.